High natural prevalence of a fungal prion

Prions are infectious proteins that cause fatal diseases in mammals. Prions have also been found in fungi, but studies on their role in nature are scarce. The proposed biological function of fungal prions is debated and varies from detrimental to benign or even beneficial. [Het-s] is a prion of the fungus Podospora anserina. The het-s locus exists as two antagonistic alleles that constitute an allorecognition system: the het-s allele encoding the protein variant capable of prion formation and the het-S allele encoding a protein variant that cannot form a prion. We document here that het-s alleles, capable of prion formation, are nearly twice as frequent as het-S alleles in a natural population of 112 individuals. Then, we report a 92% prevalence of [Het-s] prion infection among the het-s isolates and find evidence of the role of the [Het-s]/het-S allorecognition system on the incidence of infection by a deleterious senescence plasmid. We explain the het-s/het-S allele ratios by the existence of two selective forces operating at different levels. We propose that during the somatic stage, the role of [Het-s]/HET-S in allorecognition leads to frequency-dependent selection for which an equilibrated frequency would be optimal. However, in the sexual cycle, the [Het-s] prion causes meiotic drive favoring the het-s allele. Our findings indicate that [Het-s] is a selected and, therefore, widespread prion whose activity as selfish genetic element is counteracted by balancing selection for allorecognition polymorphism.     

Multimodal imaging for improved diagnosis and treatment of cancers

The authors review methods for image‐guided diagnosis and therapy that increase precision in the detection, characterization, and localization of many forms of cancer to achieve optimal target definition and complete resection or ablation. A new model of translational, clinical, image‐guided therapy research is presented, and the Advanced Multimodality Image‐Guided Operating (AMIGO) suite is described. AMIGO was conceived and designed to allow for the full integration of imaging in cancer diagnosis and treatment. Examples are drawn from over 500 procedures performed on brain, neck, spine, thorax (breast, lung), and pelvis (prostate and gynecologic) areas and are used to describe how they address some of the many challenges of treating brain, prostate, and lung tumors. Cancer 2015;121:817–827. © 2014 American Cancer Society.     

Healthy lifestyle index and risk of gastric adenocarcinoma in the EPIC cohort study

Several modifiable lifestyle factors, including smoking, alcohol, certain dietary factors and weight are independently associated with gastric cancer (GC); however, their combined impact on GC risk is unknown. We constructed a healthy lifestyle index to investigate the joint influence of these behaviors on GC risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The analysis included 461,550 participants (662 first incident GC cases) with a mean follow‐up of 11.4 years. A healthy lifestyle index was constructed, assigning 1 point for each healthy behavior related to smoking status, alcohol consumption and diet quality (represented by the Mediterranean diet) for assessing overall GC and also body mass index for cardia GC and 0 points otherwise. Risk of GC was calculated using Cox proportional hazards regression models while adjusting for relevant confounders. The highest versus lowest score in the healthy lifestyle index was associated with a significant lower risk of GC, by 51% overall (HR 0.49 95% CI 0.35, 0.70), by 77% for cardia GC (HR 0.23 95% CI 0.08, 0.68) and by 47% for noncardia GC (HR 0.53 (95% CI 0.32, 0.87), p‐trends<0.001. Population attributable risk calculations showed that 18.8% of all GC and 62.4% of cardia GC cases could have been prevented if participants in this population had followed the healthy lifestyle behaviors of this index. Adopting several healthy lifestyle behaviors including not smoking, limiting alcohol consumption, eating a healthy diet and maintaining a normal weight is associated with a large decreased risk of GC.     

Morbidity and mortality of pancreatic tumors undergoing surgical treatment

Background

Pancreatic cancer has a high mortality rate due to late diagnosis and aggressive behavior. The prognosis is poor, with 5-year survival occurring in less than 5% of cases.

Aim

To analyze demographic characteristics, comorbidities, type of procedure and early postoperative complications of patients with pancreatic cancer submitted to surgical treatment.

Methods

Cross-sectional study with analysis of 28 medical records of patients with malignant tumors of the pancreas in a 62 month. Data collection was performed from the medical records of the hospital.

Results

Of the total, 53,6% were male and the mean age was 60.25 years. According to the procedure, 53,6% was submitted to duodenopancreactectomy the remainder to biliodigestive derivation or distal pancreatectomy. The ductal adenocarcinoma occurred in 82,1% and 92,9% of tumors were located in the pancreatic head. Early postoperative complications occurred in 64,3% of cases and the most prevalent was intra-abdominal abscess (32,1%). Among duodenopancreactectomies 77,8% had early postoperative complications.

Conclusion

Its necessary to encourage early detection of tumors of the pancreas to raise the number operations with curative intent. Refinements in surgical techniques and surgical teams can diminish postoperative complications and, so, operative morbimortality can also decrease over time.     

Epigenome-Wide Association Study of Fasting Measures of Glucose,Insulin, and HOMA-IR in the Genetics of Lipid Lowering Drugs and Diet Network Study

Known genetic susceptibility loci for type 2 diabetes (T2D) explain only a small proportion of heritable T2D risk. We hypothesize that DNA methylation patterns may contribute to variation in diabetes-related risk factors, and this epigenetic variation across the genome can contribute to the missing heritability in T2D and related metabolic traits. We conducted an epigenome-wide association study for fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) among 837 nondiabetic participants in the Genetics of Lipid Lowering Drugs and Diet Network study, divided into discovery (N = 544) and replication (N = 293) stages. Cytosine guanine dinucleotide (CpG) methylation at ∼470,000 CpG sites was assayed in CD4⁺ T cells using the Illumina Infinium HumanMethylation 450 Beadchip. We fit a mixed model with the methylation status of each CpG as the dependent variable, adjusting for age, sex, study site, and T-cell purity as fixed-effects and family structure as a random-effect. A Bonferroni corrected P value of 1.1 × 10⁻⁷ was considered significant in the discovery stage. Significant associations were tested in the replication stage using identical models. Methylation of a CpG site in ABCG1 on chromosome 21 was significantly associated with insulin (P = 1.83 × 10⁻⁷) and HOMA-IR (P = 1.60 × 10⁻⁹). Another site in the same gene was significant for HOMA-IR and of borderline significance for insulin (P = 1.29 × 10⁻⁷ and P = 3.36 × 10⁻⁶, respectively). Associations with the top two signals replicated for insulin and HOMA-IR (P = 5.75 × 10⁻³ and P = 3.35 × 10⁻², respectively). Our findings suggest that methylation of a CpG site within ABCG1 is associated with fasting insulin and merits further evaluation as a novel disease risk marker.Candidate gene and genome-wide association studies (GWAS) have identified a number of sequence variants that explain some of the interindividual variation in the susceptibility for type 2 diabetes (T2D) (1,2). However, a large component of heritable T2D risk remains poorly understood, with less than half of total genetic variation explained by known single nucleotide polymorphisms (SNPs), a problem known as missing heritability (3–6). T2D is a complex and heterogeneous disease, in which disease onset and development are dependent on interactions between different genetic and environmental factors (7). Epigenetic variation, whether intrinsic or altered by environmental exposure, contributes to variation in gene expression and risk for metabolic disease (8). Furthermore, Liu et al. (9) and others (10,11) have suggested that genetic and epigenetic modifications could interact biologically and that methylation analysis might uncover heritable genetic variants contributing to disease that are difficult to tease out of conventional GWAS results. Ultimately, T2D susceptibility in humans is likely to depend on both genetic and epigenetic mechanisms (8,12–14).Studies of diabetes-related traits (e.g., fasting glucose and fasting insulin) in healthy individuals have been shown to be a fruitful approach for identifying T2D risk loci (15). Hence, for the current analysis, we examined epigenome-wide methylation associations (EWAS) for fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) in nondiabetic subjects from the Genetics of Lipid Lowering Drugs and Diet Network Study (GOLDN). We were also interested in the role of SNP variation in significant EWAS regions. Additionally, as previous studies have identified correlations between genetic variation and the quantitative trait of DNA methylation enriched at nearby loci (cis-meQTLs) (15), we integrated regional GWAS data with significant epigenetic findings for a uniquely comprehensive analysis of variation in metabolic traits.     

Improvement of Older Women's Sexuality Through Emancipatory Education

The purpose of this action research (AR) was to explore the ways in which sexuality is experienced daily and to improve the expression of older women's sexuality. The pedagogy of autonomy as proposed by the Brazilian educator Paulo Freire theoretically supported this AR, with the participation of six older adult women living in a rural setting in southwest Brazil. The older women's experiences regarding sexuality, their concerns, and their educational demands could be summarized through five phrases: the improvement of self-esteem as a way to promote sexuality; sexuality impaired by loneliness and lack of affection; men's sexual satisfaction seen as a woman's obligation; women's sexuality controlled by the society; and relinquishment of the companion to attend to the expectations of family members. Dialogical and participative educational approaches and continuous observation-participation strategies were performed to support the women's care and educational requirements.     

Applicability of Two International Risk Scores in Cardiac Surgery in a Reference Center in Brazil

Background

The applicability of international risk scores in heart surgery (HS) is not well defined in centers outside of North America and Europe.

Objective

To evaluate the capacity of the Parsonnet Bernstein 2000 (BP) and EuroSCORE (ES) in predicting in-hospital mortality (IHM) in patients undergoing HS at a reference hospital in Brazil and to identify risk predictors (RP).

Methods

Retrospective cohort study of 1,065 patients, with 60.3% patients underwent coronary artery bypass grafting (CABG), 32.7%, valve surgery and 7.0%, CABG combined with valve surgery. Additive and logistic scores models, the area under the ROC (Receiver Operating Characteristic) curve (AUC) and the standardized mortality ratio (SMR) were calculated. Multivariate logistic regression was performed to identify the RP.

Results

Overall mortality was 7.8%. The baseline characteristics of the patients were significantly different in relation to BP and ES. AUCs of the logistic and additive BP were 0.72 (95% CI, from 0.66 to 0.78 p = 0.74), and of ES they were 0.73 (95% CI; 0.67 to 0.79 p = 0.80). The calculation of the SMR in BP was 1.59 (95% CI; 1.27 to 1.99) and in ES, 1.43 (95% CI; 1.14 to 1.79). Seven RP of IHM were identified: age, serum creatinine > 2.26 mg/dL, active endocarditis, systolic pulmonary arterial pressure > 60 mmHg, one or more previous HS, CABG combined with valve surgery and diabetes mellitus.

Conclusion

Local scores, based on the real situation of local populations, must be developed for better assessment of risk in cardiac surgery.     

Spectral Analysis Related to Bare-Metal and Drug-Eluting Coronary Stent Implantation

Background

The autonomic nervous system plays a central role in cardiovascular regulation; sympathetic activation occurs during myocardial ischemia.

Objective

To assess the spectral analysis of heart rate variability during stent implantation, comparing the types of stent.

Methods

This study assessed 61 patients (mean age, 64.0 years; 35 men) with ischemic heart disease and indication for stenting. Stent implantation was performed under Holter monitoring to record the spectral analysis of heart rate variability (Fourier transform), measuring the low-frequency (LF) and high-frequency (HF) components, and the LF/HF ratio before and during the procedure.

Results

Bare-metal stent was implanted in 34 patients, while the others received drug-eluting stents. The right coronary artery was approached in 21 patients, the left anterior descending, in 28, and the circumflex, in 9. As compared with the pre-stenting period, all patients showed an increase in LF and HF during stent implantation (658 versus 185 ms2, p = 0.00; 322 versus 121, p = 0.00, respectively), with no change in LF/HF. During stent implantation, LF was 864 ms2 in patients with bare-metal stents, and 398 ms2 in those with drug-eluting stents (p = 0.00). The spectral analysis of heart rate variability showed no association with diabetes mellitus, family history, clinical presentation, beta-blockers, age, and vessel or its segment.

Conclusions

Stent implantation resulted in concomitant sympathetic and vagal activations. Diabetes mellitus, use of beta-blockers, and the vessel approached showed no influence on the spectral analysis of heart rate variability. Sympathetic activation was lower during the implantation of drug-eluting stents.     

Surgical treatment of non-cystic fibrosis bronchiectasis in Brazilian children

Purpose

To determine the clinical characteristics of patients submitted to surgical treatment for non-cystic fibrosis (CF) bronchiectasis, the indications for surgery, and the results obtained at a referral facility for pediatric thoracic surgery.

Methods

Between January 1998 and December 2009, we retrospectively reviewed the medical charts of 109 pediatric patients with non-CF bronchiectasis who underwent surgical treatment. These findings were subsequently analyzed by focusing on postoperative complications and long-term results.

Results

Of the 109 patients undergoing pulmonary resection, the mean age was 7.6 years (ranging from 1 to 15.5 y–o) with male predominance (59 %). The most common procedure was segmentectomy (43 %) followed by left lower lobectomy (38 %). Minor postoperative complications occurred in 36 % of the patients; the most common was transient atelectasis (26 %), followed by air leak (6 %), and postoperative pain (4 %). There was one death within the 30-day postoperative period, but it was unrelated to the procedure. Eighty-three children were followed after discharge, with a mean follow-up period of 667 days. Sixty-five (76 %) patients showed improvement of clinical symptoms after surgery.

Conclusions

Lung resection for the treatment of non-CF bronchiectasis in children is a safe procedure, with no life-treating morbidity and low mortality. This procedure also leads to significant improvements in symptoms and quality of life.